When the lumen of an artery is partially restricted by an extrinsic or intrinsic obstacle (stenosis), changes occur in the blood flow as welll as in the mechanical strains placed upon the arterial wall. We plan to study these phenomena and their consequences (a) in living models of arterial stenosis (including spasm) and (b) in mechanical flow systems. Our principal living model will be the stenotic aorta of the rat. Stenosis will be produced by several extrinsic means, for periods ranging from 5 min. to 3000 days; its effects will be studied by light as well as by transmission and scanning electron microscopy, at, above and below the stenosis; special attention will be given to the phenomenon of post-stenotic dilatation. The acute intimal changes will be quantitated by means of a morphometric method. Since these acute intimal changes represent a readily measurable response to injury, they will be used to determine whether the arterial response is affected by systemic conditions or by drugs known to affect the endothelium (spontaneous (rat) diabetes, hypertension, hyperlipemia, thrombocytopenia, heparin, aspirin). Stenosis will also be studied in dog arteries large enough to allow measurements of pressure and flow, and thus to calculate the shear stress on the endothelium. Another type of stenosis will be produced (in rats as well as in dogs) by spasm, a potential cause of arterial disease. Spasm will be induced with drugs and by electrical stimulation. In parallel studies, scaled flow models will be constructed which will provide qualitative and quantitative data on the disturbances of flow occurring in the living stenotic arteries. The mechanisms underlying post-stenotic dilatation will also be studied.